Do Age-Related Changes in the Gut Microbiota Contribute to the Loss of Muscle Growth in Response to Protein Intake?

Sarcopenia is the name given to the age-related loss of muscle mass and strength. There are many potential causes of this decline with at least some supporting evidence in the scientific literature. The most compelling are those related to loss of stem cell function, but there is also the question of whether or not older individuals lose the ability to process dietary proteins to produce new muscle tissue. In particular dysfunction in processing of the essential amino acid leucine is a possible mechanism, and some groups have considered dietary leucine supplementation as a possible compensatory treatment. The open access paper here ties in recent findings regarding age-related changes in the microbial populations of the gut to the issue of protein processing in aging. It is by no means settled as to whether or not all of this will fit together sufficiently well to explain a significant fraction of sarcopenia, but it is certainly an active area of research.

Sarcopenia is a geriatric syndrome defined as the age-related loss of skeletal muscle mass and function, quantified by objective measures of muscle mass, strength, and physical function. One major risk factor for the development of sarcopenia is protein-energy malnutrition. A number of factors can lead to reduced protein intake in older age. Patients with sarcopenia are often frail (vulnerable to minor stressors) and the two concepts (frailty and sarcopenia) share an increased risk of adverse outcomes. Three large observational studies have supported an association between protein intake and muscle strength and mass, but multiple trials carried out in healthy, replete, older adults, without an exercise intervention, have been negative.

In those with suboptimal protein intake, the most promising results are for specific essential amino acids, particularly leucine, but also its metabolite β-hydroxy β-methylbutyric acid (HMB). Supplementation with these more targeted regulators of muscle protein synthesis (MPS) may be most effective for overcoming anabolic resistance in this cohort, especially if combined with exercise, a potent stimulator of anabolic response in muscle at all ages. Anabolic resistance refers to the phenomenon whereby older adults require a higher dose of protein to achieve the same response in MPS as a younger adult. The aetiologies and mechanisms for this are not understood, but we propose that the gut microbiome may be implicated in one or many of those suggested in the literature.

With age and frailty in particular, the resilience of the gut microbiome is reduced, as it becomes more vulnerable to medications, disease, and changes in lifestyle, with changed species richness and increased inter-individual variability. Ageing is associated with chronic inflammation, often referred to as 'inflammaging'. Here we suggest that this 'inflammaging', in combination with altered gut microbiome composition and/or diversity, leads to changes in protein metabolism, absorption and availability; ultimately contributing to anabolic resistance and therefore to reduced MPS and the development of sarcopenia.